Rh Disease

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Synonyms of Rh Disease

Congenital Anemia of Newborn

Erythroblastosis Fetalis

Erythroblastosis Neonatorum

Hemolytic Anemia of Newborn

Hemolytic Disease of Newborn

Icterus Gravis Neonatorum

Rhesus Incompatibility

Rh Factor Incompatibility

Rh Incompatibility

Disorder Subdivisions

No subdivisions found.

General Discussion

Rh disease or Rh incompatibility (also known as erythroblastosis fetalis) occurs when a woman with Rh-negative blood conceives a child with Rh-positive blood. Red blood cells are destroyed (hemolysis) because of this incompatibility, leading to anemia and other symptoms in the infant. Symptoms vary in severity among affected infants and may include an unusual yellowish coloration of the skin (jaundice); swelling of the chest and abdomen due to the accumulation of fluid (edema); and/or a pale appearance of the skin. In more severe cases, affected infants may have experience life-threatening complications. Rh disease occurs only when a mother's blood is Rh-negative and her baby's blood is Rh-positive.

Symptoms

During the first pregnancy of an Rh-negative woman carrying an Rh-positive fetus, there are rarely any symptoms. However, the risks of sensitization increase with each subsequent pregnancy when the fetus is Rh-positive.

In Rh disease, red blood cells from the fetus cross the placenta and enter into the mother's circulation during pregnancy. This stimulates maternal antibody formation against the Rh factor. These antibodies reach the fetus via the placenta and cause destruction of the fetal red blood cells (hemolysis). This consequently causes anemia in the fetus. To overcome this anemia, the fetal bone marrow releases immature red blood cells (erythroblasts) into the fetal circulation. The hemoglobin from the destroyed red blood cells is broken down to bilirubin, which is cleared from the fetal circulation by crossing the placenta into the mother's blood. After birth, however, bilirubin builds up in the newborn's circulation and high levels of bilirubin may sometimes be deposited in the basal ganglia of the brain causing Kernicterus. (For more information, please choose "kernicterus" as your search term in the Rare Disease Database.)

In women who have developed Rh-sensitization, succeeding pregnancies with Rh incompatibility produce progressively more seriously affected infants, unless treatment with an anti-Rh-gammaglobulin (RhoGAM) is given to the mother within 72 hours after each childbirth or termination of pregnancy. The more severely affected fetuses develop profound anemia in the womb and are delivered with gross edema (swelling) of the entire body (hydrops fetalis). This may be suspected before delivery if excessive fluid around the fetus in the amnion sac (polyhydramnios) is present (detected through x- rays). Sometimes a picture of the fetus in the uterus (amniogram) reveals severe scalp edema.

Newborn infants with Rh disease are extremely pale and may have severe generalized edema, including the presence of liquid in the pleural cavity around the lungs (pleural effusion) and an accumulation of serous fluid in the abdominal cavity (ascites). The liver and spleen are enlarged because of production of red blood cells outside the bone marrow. Congestive heart failure may sometimes occur. Because of anemia and prematurity, lack of oxygen in the lungs (asphyxia) is likely during labor and delivery. The prematurity and asphyxia along with an abnormal decrease of the amount of protein in the blood (hypoproteinemia) may predispose the infant to respiratory distress syndrome (RDS), the signs of which may be difficult to distinguish from those of congestive heart failure.

Less severely affected newborn infants may be anemic, but do not have edema or other signs of hydrops. Others may have little or no anemia at birth. Affected infants usually develop severe hyperbilirubinemia shortly after delivery because of the continuing hemolytic effect of Rh-antibodies that have crossed the placenta.

Succeeding pregnancies tend to produce more seriously affected fetuses. Erythroblastosis can be prevented by injecting the mother with a high-titer anti-Rh-gammaglobulin preparation within 72 hours after delivery to prevent her from developing antibodies.

Causes

Rh incompatibility occurs when a woman with Rh-negative blood conceives a child with Rh-positive blood. Red blood cells from the fetus cross the placenta and enter into the mother's circulation stimulating maternal antibody formation against the Rh factor. These antibodies reach the fetus via the placenta and cause destruction of the fetal red blood cells, consequently causing anemia and bilirubin in the fetal blood (jaundice) which makes the infant appear yellow. Rh-negative and -positive blood types are determined by genetic factors.

Affected Populations

Since the introduction of Rh immunoglobulin as a treatment for Rh disease in 1968, the number of babies born with the disorder has dropped dramatically from greater than 20,000 babies per year in the United Sates to approximately 4,000 babies per year.

Rh disease occurs only in infants who have Rh-positive blood and whose mothers have Rh-negative blood. Some clinicians estimate that in the U.S. only about 13% of marriages result in pairing of an Rh-positive man and an Rh-negative woman. They estimate that one in about 27 children born to these couples will suffer from Rh disease.

Related Disorders

Idiopathic autoimmune hemolytic anemia is an acquired disease that occurs when antibodies form against a person's own red blood cells. In the idiopathic form of this disease, the cause is unknown. There are other types of immune hemolytic anemias where the cause may result from an underlying disease or medication. Idiopathic autoimmune hemolytic anemia accounts for one-half of all immune hemolytic anemias. The onset of the disease may be quite rapid and very serious.

Fetomaternal hemorrhage (FMH) is a common occurrence in pregnant women and is most often associated with small volumes of blood transferred across the placenta. Chronic fetomaternal hemorrhage leads to autoimmunization of Rh-negative mothers, resulting in an increased risk of hemolytic disease of the newborn. Massive FMH involving larger volumes of blood can become life-threatening. The signs and symptoms are decreased movement, sinusoidal heart rhythms, or fetal anomalies.

Kernicterus is a condition characterized by an excess of bilirubin in the blood that is deposited in the basal ganglia of the brain and in the brainstem nuclei. (For more information, choose "Kernicterus" as your search term in the Rare Disease database.)

Standard Therapies

The blood group of the mother can be determined conveniently and with ease. If the mother's blood is found to be Rh-positive, there is no chance of the baby being born with Rh disease. If the mother's blood is found to be Rh-negative, the father's blood group must be determined. If the father's blood group turns out to be Rh-positive, there is a chance that the fetus will be Rh incompatible. In such cases, or if the father is unavailable for testing, a sample of fetal blood is taken in order to determine if Rh incompatibility is present.

Treatment
All Rh-negative mothers of Rh-positive babies should receive two injections of a biological known as Rh immune globulin (RhIG). The first should be administered at about the 28th week of pregnancy. The second should be given within 72 hours after delivery.

There have been major improvements in the treatment of fetuses with severe Rh disease. Newer treatments involve blood transfusions usually using cordocentesis. This involves using a fine, hollow needle under the guidance of an ultrasound.

An infant with hydrops fetalis or severe erythroblastosis fetalis (without hydrops) due to Rh disease is usually critically ill and should be treated in a perinatal intensive care facility whenever possible. Fetal heart rate should be monitored during labor. If signs of lack of oxygen (asphyxia) occur, or if the infant is severely affected, cesarean section delivery should be performed. The mainstay of treatment is exchange transfusion. This is a blood transfusion using twice the infant's calculated blood volume which removes 85% of the infant's blood, including circulating antibodies, sensitized red blood cells, accumulated bilirubin, and replenishes red blood cells.

Investigational Therapies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office: